The overall objectives of this project are to understand the endocrinology of the human glycoprotein hormones, thyroid-stimulating hormone (TSH), choriogonadotropin (hCG), luteinizing hormone (LH), and follicle-stimulating hormone (FSH), and thereby to develop diagnostic and therapeutic clinical applications. Recent research advances include the following: Identification of novel molecular structures in the oligosaccharide moieties of the human choriogonadotropin and free alpha-subunit of pregnancy; demonstration of a deficiency in the normal physiological pattern of thyrotropin secretion in patients with hypothalamic and/or pituitary diseases; and demonstration that the oligosaccharide moieties of thyrotropin play an essential role in the activation of the adenylate cyclase second messenger system. Future directions of the project will include assessment of the functional impact of proteolytic digestion of the choriogonadotropin subunits, elucidation of renal mechanisms for catabolism of choriogonadotropin and related molecules, exploration of naturally-occurring antagonists to follicle-stimulating hormone, and further characterizations of the carbohydrate structure of choriogonadotropin and its subunits in pregnancy.